Otitis externa which involves the ear canal portion of the external ear is a common otologic problem occurring in humans mainly during hot and humid weather. Otitis externa is five times more frequent in swimmers than in non-swimmers. It is an acute or chronic inflammation of the epithelium of the external ear canal. It may develop anywhere from the tympanic membrane to the pinna. It is variably characterized by erythema, edema, increased sebum or exudates, and desquamation of the epithelium. In later stages, suppuration occurs in the ear canal and hearing may be decreased. Over 90% of cases of acute Otitis Externa (AOE) are due to bacterial infections.
Otitis externa is the most common disease of the ear canal in dogs and cats, and is occasionally seen in rabbits (in which it is usually due to the mite Psoroptescuniculi).
Otitis media involves infections of the middle ear and it is a very common otologic problem in adults and particularly in children. It has been estimated that nearly 95% of all children experience one or more episodes of otitis by age 9, and that about 15% of all visits by children to pediatricians are due to otitis media. In children, the disease is often associated with upper respiratory afflictions which trigger a transudate secretion response in the Eustachian tube and middle ear. Bacteria and viruses migrate from the naso-pharynx to the middle ear via the Eustachian tube, and can cause the Eustachian tube to become blocked, preventing ventilation and drainage of the middle ear.
The common treatment of AOE consists of topical antibiotics, with or without steroids, analgesia and water avoidance. Otic preparations are generally supplied in the form of ear drops. Antibiotic agents in ear drops include aminoglycosides (mainly neomycin) in combination with polymyxin B and hydrocortisone or fluoroquinolones such as ciprofloxacin and ofloxacin.
Ciprofloxacin is a safe and efficacious antibacterial fluoroquinolone active against a broad spectrum of gram-positive and gram-negative bacteria. Ciprofloxacin is present as Ciprofloxacin base and Ciprofloxacin HCl.
Due to its proven safety and lack of ototoxicity, sterile ciprofloxacin ear drops are prescribed to treat patients with AOE with intact or non-intact tympanic membrane. Topical otic compositions containing a combination of either ciprofloxacin and hydrocortisone or ciprofloxacin and dexamethasone are sold under the name of CIPRO HC™ and CIPRODEX™, respectively, by Alcon Laboratories, Inc.
U.S. Pat. No. 5,843,930 to Purwar et al. discloses a liquid non-ototoxic, topical, otic pharmaceutical composition for the treatment of otitis externa and otitis media which comprises ciprofloxacin, a non-ionic viscosity augmenter, a preservative, water sufficient to produce an aqueous composition, hydrocortisone in aqueous suspension, lecithin, and polysorbate 20 to 80. U.S. Pat. No. 5,843,930 further discloses methods for treating otitis which comprise administering the otic pharmaceutical composition topically into the ear.
U.S. Pat. No. 6,359,016 to Singh et al., discloses aqueous suspension formulations comprising ciprofloxacin, dexamethasone, sodium chloride as an ionic tonicity agent, a nonionic polymer, and a nonionic surfactant. The formulations according to U.S. Pat. No. 6,359,016 have a pH from 3-5 that can be adjusted by NaOH/HCl and comprise the buffering system of sodium acetate and acetic acid. According to U.S. Pat. No. 6,359,016, the formulations may further comprise quaternary ammonium halide as a preservative and a chelating agent.
U.S. Pat. No. 6,462,033 to Singh discloses method for preparing a topical composition comprising ciprofloxacin and hydrocortisone. The compositions of U.S. Pat. No. 6,462,033 have excellent physical stability attributed to the method of their preparation, i.e., hydrocortisone is dispersed with lecithin and optionally with a polysorbate surfactant for greater than 45 minutes prior to combining hydrocortisone with the remainder of the composition.
U.S. Pat. No. 6,730,288 to Abram discloses pharmaceutical aerosol foam compositions which include a pharmaceutically active ingredient, an occlusive agent, an aqueous solvent, and an organic cosolvent, wherein the pharmaceutically active ingredient being insoluble in both water and the occlusive agent. The pharmaceutical compositions according to U.S. Pat. No. 6,730,288 are useful for topical administration of the pharmaceutically active ingredients on the skin.
U.S. Pat. No. 7,078,058 to Jones et al. discloses foamable pharmaceutical compositions comprising a corticosteroid, a quick-break foaming agent, a propellant and a buffering agent. According to U.S. Pat. No. 7,078,058, the quick-break foaming agent comprises an aliphatic alcohol, water, a fatty alcohol and a surface active agent. The compositions of U.S. Pat. No. 7,078,058 are especially well-suited for use in the treatment of various skin diseases, and in particularly in the treatment of scalp psoriasis.
U.S. Pat. No. 7,186,416 to Popp et al. discloses foamable delivery systems which comprise a solvent composition, a surfactant composition, a propellant and an acid, particularly useful for dermatological administration of corticosteroids and antifungal agents.
U.S. Pat. No. 7,700,076 to Tamarkin et al. discloses an alcohol-free cosmetic or pharmaceutical foam composition comprising water, a hydrophobic solvent, a surface-active agent, a gelling agent, an active component selected from the group of urea, hydroxyl acid, and a therapeutic enhancer and a propellant. The foam according to U.S. Pat. No. 7,700,076 further comprises active agents and excipients with therapeutic properties having enhanced skin penetration.
U.S. Pat. No. 8,030,362 to Eilat discloses a pharmaceutical composition for the treatment of an ear disorder in a form selected from foam and mousse comprising: a pharmaceutical agent known to affect an ear disorder; a pharmaceutically acceptable carrier comprising a dispersing agent that is a foam forming agent; and a dispensing device adapted for the dispensing of the pharmaceutical agent admixed with the carrier to the external auditory meatus.
International Patent Application Publication No. WO 2010/143186 assigned to the applicant of the present invention discloses a foamable otic pharmaceutical composition comprising an oil-in-water emulsion which comprises a fluoroquinolone, a hydrophobic solvent, an emulsifier and/or a synthetic surfactant, a stabilizing agent, a polar co-solvent, and water; and a compressed propellant gas, wherein the composition packaged in a container is adapted to form foam after dispensing from the container, the foam having a density of about 0.1 gr/ml to about 0.5 gr/ml.
U.S. Patent Application Publication No. 2006/0233721 discloses a foamable oil-in-water emulsion composition which includes: (a) an oil globule system selected from the group consisting of oil bodies and sub-micron oil globules; (b) about 0.1% to about 5% by weight of at least one stabilizing agent selected from the group consisting of a non-ionic surfactant having an HLB value between 9 and 16, an ionic surfactant, and a polymeric agent; and (c) a liquefied or compressed gas propellant.
There is an unmet need for formulations comprising clinically efficacious compositions of an antibiotic agent which upon dispensing from a container form a stable dosage form retained in the patient's ear so as to treat ear disorders.